Category: Multiple Sclerosis

I explore in the studies of the website about the burden of multiple sclerosis in the web that I found the expenses of multiple sclerosis depend on many factors and we must know the cause of the wide ranges of the expenses in the market and the number of patient infected by multiple sclerosis about approximately above 4o,ooo patient in Egypt

By the who, it shows that each 100000 people that there are 30 from will be diseased (2).

In Egypt It is found many studies about multiple sclerosis:

In2008: the newest study of multiple sclerosis in Egypt by the office of health saw that the disease represent 1.4 % of all neurological illness and the total number of patients all over countries are range from 25,000-to 40000 and the health care need support with money to be able to use high-cost medication that because the office health cannot cover more than 50% of the expensive medications (3). Dr. Samira Ashour, the head of the neurology department at AIN shams university: said patient costs from 2,000 LE to 3,000 LE for 3-6 months for treatment to be cured (2)(4).

It was, unfortunately, some people are unable to buy for treatment because it is the cost is high around 4,000 EGP which makes them unable to continue treatment. While Dr. Abel Ghany talks about the awareness of the cost of the disease and said that Egyptian medical insurance only grant a recompense 2000 LE to a patient per month that cover a small amount of the cost of illness, where all costs of illness between 70,000 LE to 140,000 LE per year for a patient, the researches in the neighbor country like united statue that In 1990: the expenses for treatment from multiple sclerosis are nearly 9000$ to 12,000$ for the patient per year the agent go on developing and increase in price while in 2004 the range of burden for sick was 16,050$ , THE total cost of care and exploit of service increase not only with high and good effect but also with increasing cost range in health care ; the cost for moderate relapse intensity function and lack of ability is 30,000$ and with high relapse intensity and inability 50,000$ and with sever inability cost 100,000$. And the other recent study in 2012: as average expense of illness was 30,000$ per year (5).

In determining The cost of illness in Egypt is higher than found in the united statue, this because of the increase of population and unemployment in Egypt that effect than in united statue.

However, the medical economic journal find the expenses of multiple sclerosis in health care between (8,500$ and 50,000$) increase every year and the normal cost of illness from 8ooo$ to 11ooo$ compared with the now the cost of illness about 60,000$ annually (1).

Newly, the new drug amended for treatment cost for multiple sclerosis that commonly enter market range between 25 – 6o% are higher compared with the abundant drug amended for treatment.

Direct medical cost & the Indirect medical cost represents 93.1% 6.9% over the total cost that is the direct medical cost is range between less than 15,000$ to higher than 50,000$ annually which is larger compared with the indirect medical cost which are in between from 3726$ to 19264$ and the costs of outpatient visit is 3,443$ which is higher than The prescription (DMC) which cost is 1834$ and the inpatient hospitslization:1546$.

The problem increased as 46% of their loss their job and their expenses of them increase by around 3.3 fold and days patient stayed in bed increased around 4.4 fold that all are compared with the middle east and the worldwide, as in middle east the exiting of multiple sclerosis are in 5 eastern countries, that the spread of disease observed increasing significantly in a recent decade than the past as the Interferon was the most treatment use Egypt and MRI scanner lower use in the middle east they need more research about other treatment and in worldwide multiple sclerosis affect around 2.5000000 patient (6).

Introduction

Multiple Sclerosis:

Multiple Sclerosis (MS) defined as a demyelinating disease of the central nervous system (Faezah, 2020)(Printza, 2019). A possibility to be an autoimmune neurological disease (Aghaz, 2018). M.S could involved motor, sensory, cognitive limitations in addition to swallowing and problems in communication (Barrera, 2019)(El-Wahsh, 2019). a long-lasting progressive disease (Solaro, 2019).

MS could be classified as, Relapsing Remitting MS (RRMS), Secondary Progressive MS (SPMS), Primary Progressive MS (PPMS) and Progressive Relapsing MS (PRMS) (Alali, 2018). Moreover, losing the myelin and gliosis formating also justificated this classifing (Moradi, 2017).

Dysphagia:

Any disorder including limited or weakness in the swallowing skills recognized as dysphagia (Elif, 2018). Also any disturbaing for the normal function of swallowing (Maryam, 2017). Both of problems can lead to a severe issues such as aspiration pneumonia, dehydration, malnutrition, and life quality deterioration (Giuseppe, 2018).

Dysphagia mostly accompanied with physical ability and quality of life impacts (Printza, 2018)(Vogel, 2017). Swallowing sometimes called Deglutition, describing the transfering steps of food and liquids (Dalal, 2017).

Oropharyngeal dysphagia (OD) could lead to challenges in life aspects (Bartlett, 2018) and a real impairment in the safety and efficiency (Olga, 2019)(Zahra, 2018). Swallowing process had different stages: the preparatory, the oral, the pharyngeal, and the esophageal stage (Eveline, 2019). Dysphagia is the most common symptom in old people and also in the neurological diseases including multiple sclerosis (Quiros, 2020).

Relation between Multiple Sclerosis and Dysphagia:

Dysphagia nominated as the highly alert and a threatening of life symptom within the multiple sclerosis (MS) population that showed an incidence between 33% and 43% (Elif, 2018).

Dramatically, 37% of the dysphagic people had a variables of severity extended from mild to severe dysphagia as the percentages; mild 50.6%; moderate 29.4%; and severe 20% (Maryam, 2017).

Deeply, people who had diagnised with a neurological diseases could face a fluctuated sitiuations of swallowing disorders among their life (Giuseppe, 2018).

Review Background:

Obviously; in this section, an overview for the literature review of the field of dysphagia screening and assessment with different pulation and neurological disorders.

Printza and others (2019) and Solaro and others (2019) aimed to detect the prevalence, attitudes and quality of life in patients with multiple sclerosis including the prevalence of dysphagia. It recommended to distingwish the swallowing difficulties with MS to confirm the early identification, effective management, prevention of complications.

Dalal and others (2018) reviewed the literature of Multiple Sclerosis which described the definition, types, frequency and symptoms of dysphagia and its impact on the quality of life. 38% of adults with MS had swallowing problems. Further invistegation required to determine whether early intervention for dysphagia can improve the swallowing function.

Alireza et al (2018) and Marissa et al (2019) were estimated and discussed the prevalence of dysphagia in general. the estimation of the general prevalence of dysphagia in MS-affected patients was 43.33%, Although dysphagia is not typically a first sign of MS, it observed in mildly impaired patients with low levels of disability and increased as the disease progress reaching as high as 65% in severely disabled individuals with MS.

Magdalena and others (2020) assessed the prevalence and characteristics of dysphagia in demyelinating diseases using the: DYMUS (DYsphagia in MUltiple Sclerosis), EAT-10 (Eating Assessment Tool) and SDQ (Swallowing Disturbance Questionnaire). The results showed that pharyngeal-stage dysphagia was observed more frequently than oral-stage dysphagia.

Maryam and others (2017) aimed to determine the prevalence of dysphagia in MS and identifying predictors associated with dysphagia. Dysphagia was evaluated using Mann Assessment of Swallowing Ability (MASA). In total, dysphagia was found in 37% of mild to severe dysphagia.

– Measurements of Dysphagia in Multiple Sclerosis.

Sarah and others (2018) developed and validated the Speech pathology-specific questionnaire for 164 persons with Multiple Sclerosis (SMS). This study was fair in results but the weak points were to do the sample collection through online and the participants formal diagnosis of MS.

Eveline and others (2019) aimed to validate the Dutch-language version of the M.D. Anderson Dysphagia Inventory (MDADI) for 178 patients with neurogenic oropharyngeal dysphagia (OD). It was strengthed hence the large sample size. The results of this study showed a validate dysphagia-questionnaire for patients with neurogenic OD.

Dysphagia of Multiple Sclerosis scale (DYMUS), had many studies that had a concentration regarding multi fields of DYMUS:

Firstly; the factor analysis, internal consistency and test–retest reliability were studied by Dalal and others (2017) Or Dalal et al 2017 against the EAT-10 on MS patients.

Additionally, translated it into Farsi by Zahra and others (2018) using Forward-backward method and then confirmatory factor analysis (CFA) was used to examine the construct validity. Internal consistency and test-retest reliability.

Moreover, a Persian version and evaluating the validity and reliability of the test on Southeast Iranian by Faezeh and others (2020) to evaluate the swallowing problems in multiple sclerosis (MS). The results indicated a good reliability and validity for patients with MS.

Furthermore, identifing the frequency and characteristics of dysphagia in multiple sclerosis patients by Sahar and others (2017), the prevalence ranged from 10% to 90% of subjects based on the dysphagia criteria of MS patients.

Elif and others (2018) aimed to support the use of the rapid and easy-use screening test of dysphagia in the early stages for turkish M.S patients.

Therefore, another adapting to Greek by Printza and others (2018) and resulted to valid use of the Greek version of DYMUS for clinical detection of dysphagia in Multiple Sclerosis.

– Other Measurements of Dysphagia.

Olga and others (2019) mentioned that the videofluoroscopy swallowing study (VFSS) and fiberoptic endoscopic evaluation of swallowing (FEES) are the most commonly used instrumental swallowing assessment techniques. It aimed to ensure evidence-based assessment of oropharyngeal dysphagia and to guide future research.

Adam Vogel and others (2017) aimed to designed the Clinical Assessment of Dysphagia in Neuro-degeneration (CADN) at 125 patients with a neurodegenerative disease. It mentioned a good score in specificity and in sensitivity were had been copied.

Kara and Kelly (2018) reviewed available screening tools with an emphasis on the literature that supported their validity and reliability. In addition reviewing the impact of dysphagia on health care costs and patient outcomes. The results revealed that many of the screens were clinician created and are lacking of validation and the incidence of dysphagia post stroke ranged from 37% to 45% using screening techniques, from 51% to 55% using clinical testing, and from 64% to 78% using instrumental testing. Recommending that the ideal screening tool should be easy to administer, inexpensive, and accurate, with consideration of the instrument’s sensitivity, specificity, and both the positive and negative predictive values.

Quiro et al (2020) designed a new scale Oropharyngeal Dysphagia Screening – for Patients and Professionals (ODS-PP) for dysphagia assessment in Spanish people in Spanish language and was translated to english language for publishing scheme, and it was validated and adapted to a large community. It is a new scale with a very strong back ground which allow more people to use it, this scale not using water or food during assessment which take more care about patient safety and more simpler to use by any care giver such as doctors, nurses and others including family related in addition to the patient, also it is very short and takes less than 3 minutes to be finished in comparison to other screening questioners which take more that 10 minutes. An advantage for this scale that it cosiderd as the first test with a high scorse in detecting OD more than EAT-10 scores.

Truly, ODS-PP was the ideal screening tool because it easy to distribute , affordable, and proper, and the higher scores of the sensitivity and specificity. Most tests of dysphagia screening were translated and adapted to many languages and communities, also some of them adapted more than once for the same language.

Accordingly, this reason the current study focused on using a new and valid scale which still not use in many language and in multi areas thus, the ODS-PP was nominated to be used hince it is only the scale in the world up to date which designed in spanish and used in spain only.

Aims of Study:

This study had a general purpose which focused on the Assessment of Dysphagia in Jordanian Arabic Speaking people from Multiple Sclerosis society, while there a specific goals were:

• To translate and adapt ODS-PP for testing dysphagia in Arabic population.
• To test dysphagia using different instruments ODS-PP and EAT-10 (Arabic version).
• To compare the new tool ODS-PP in arabic with EAT-10 for detecting dysphagia in multiple sclerosis
• To test dysphagia in Multiple Sclerosis in comparing to people without MS or any disease (Typically Healthy).

Methods:

Participants:

Participants who were part of the study being nominated from the Arabic native speakeing, both genders were included and their ages were more than 18 years old. In addition they were divided by tow groups: group one as a Multiple Sclerosis people and group tow as a Typically Healthy people those with no issues or illnesses. Sample charachteristics are shown in Table 1.

Table 1. Sample’s charateristics.

Sex Age

Male Female Mean Standard deviation Range Total N MOCA

Multiple Sclerosis 12 9 66 40,38-11,35 21-22 21 29,09

Typically Healthy 7 6 64 45,31-12,62 13-29 13 30

Preliminar analysis with Chi Square showed that there were not statistically significant differences between the groups in Sex (χ2(1) = .03, p = .565). Moreover, preliminar analysis using t-test showed there were not statistically significant differences between MS and TH (p=.25). However, for the mental and cognitive status (MOCA) there were statistically significant differences between MS and TH t(32)= -2,143; p=.04

Design and Data Analysis:

Data were collected and the Analyses were assumed using Statistical Package for the Social Sciences (SPSS), version 20. The study followed an ex post facto design. Pearson Chi-Square was used to evaluate the differences between participants in each group – MS and NH – in Sex.

MANOVA – Multivariate Analysis of variance assessed the differences for assessing the screening validity od arabic version of ODS; differences were presented as percentage and 95% confidence interval. T-Test was used to evaluate the differences between participants in each group – MS and NH – in Age.

In addition t-test was used to evaluate the differences between participants in each group – MS and NH – in Mental Cognitive state (MOCA) Statistically significant results when p < ,05.

Instruments:

– The Eating Assessment Tool / EAT-10:

Belafsky (2008) designed the english version and Farahat (2015) was adapted and validated to Arabic language at Eygeptian population. This scale considered as a world wide commonly used, it contains of 10 questions as self report test.

The Eating Assessment Tool is a self-administered, symptom-specific outcome instrument for dysphagia. Appendix 1 showed Arabic EAT-10.

– Oropharyngeal Dysphagia Scale – Profesional and Patients / ODS-PP:

Quire et el and others (2019) developed and validated a new scale for Oropharyngeal Dysphagia (OD) assessment on the spanish people. The test consists of 18 items, organized by 3 scales: Safety, Efficacy, and Others. In most of the items, the Likert scale ranged from 1 = Never to 4 = Very often.

The test had been designed to be completed either by the patient with OD (self-reporting) or the professional caring of patient’s food. Appendix 2 showed Arabic ODS-PP.

– Monterial of Cognitive Abilities / MoCA:

It was created by Nasreddine and others (2004) in English language and the developement to the Arabic version by Tamader and others (2009). The Montreal of Cognitive Assessment (MoCA) had used a breif 30 questiones which can help the health professionals to test the cognitive abilities for people. MoCA is measuring executive functions and multiple cognitive domains Appendix 3 showed Arabic MoCA.

Procedure:

After discussion with the Ethical committee supervisor of the UGR then the approval for this study was obtained.

Firstly, this study was initiated by translating the ODS-PP from spanish to Arabic language and prepared for starting the study. Then an invitations for the people were sent through a professional in speech therapy and an MS organization. Agter that we assigned an appointment for each participant with fixed time and date to collect the data. A consent form was signed for agreement of participating.

During the interview with the participant and his/her family relative, all instructions were explained and the forms were shown to them, immediatley the results collected as:

• Step one, the participant completed the MOCA scale in Arabic.
• Step tow, the participant completed the ODS-PP scale in Arabic.
• Step three, the participants completed the EAT-10 scale in Arabic.
• Step four, collecting all results and confirmed the completed forms from all participants.

Results:

MANOVA results have shown that there was a statistically significant effect of Group – Mean Effect, F(4,29) = 4.518; p = .01; η2= .38, sp. = .9, which indicated that the MS group showed higher scores in both tests that the TH group. Results for EAT-10 and ODS-PP were shown in Table 2.

Between subjects analysis showed that there were a statistically significant effect of Group – in each one of the measures.

There were statistically significant differences in the EAT-10 F(1,3030) = 18.526; p < .0001; η2= .37; sp.=.99; the group MS showed higher scores than TH.

There were statistically significant differences in the ODS-PP, total score, F(1,3779) = 13,611; p < .001; η2= .30; sp.=.95; the group MS showed higher scores than TH.

There were statistically significant differences in the ODS-PP category Security F(1,1202) = 12,487; p < .001; η2= .28; sp.=.93; the group MS showed higher scores than TH.

There were statistically significant differences in the ODS-PP category Efficiency F(1,326) = 13,396; p < .001; η2= .30; sp.=.94; the group MS showed higher scores than TH.

There were statistically significant differences in the ODS-PP category Others F(1,76) = 15,907; p < .0001; η2= .33; sp.=.98; the group MS showed higher scores than TH.

Table 2. showed the Results for EAT-10 and ODS-PP .

Measure Group N Mean Standard F p Effect size Observed

deviation power

Total EAT-10 MS 21 19,43 16,18 18.526 .0001 .37 .99

TH 13 0 0

Total ODS-PP MS 21 40,62 21,08 13,61 .001 .30 .95

TH 13 18,92 0,28

Total Security MS 21 22,23 12,41 12,49 .001 .28 .93

TH 13 10 0

Total Eficiency MS 21 11,39 6,24 13,4 .001 .30 .94

TH 13 5 0

Total Others MS 21 7 2,76 15,91 .0001 .33 .98

TH 13 3,92 0,28

Study Concurrent Correlations:

Pearson’s correlation coefficients were calculated for determining the concurrent validity between the ODS-PP and the EAT-10. For these analyses, only results of the group M.S were considered. The correlation matrix was shown in Table 3.

Results showed significant correlations in most of the item’s of the ODS-PP with the EAT-10 test item’s (correlations ranged from r = .574 to r = 901, p = 0.001). There was an exception with the ODS-PP item 18. see table 3 for more details.

Chronic demyelinating condition is a definition for multiple sclerosis (MS). It is the most common recurrent CNS condition in young adults in the United States and has an incidence of 1 in 1000. It is marked for many years by exacerbations and remissions. At the middle age of 30, females are almost half as often as males, it becomes symptomatic.

MS is uncertain etiology but probably involves genetic predisposition and immune failure. MS is a temperate climate disorder in particular. Persons emigrating to more temperate endemic areas from regions with a low prevalence before the age of 15 expect an increased risk, which means that environmental factors are significant. The disorder has family-related aggregates, with an increased risk in MS diagnosed in second and third grades and 25% concordance of monozygotic twins for MS. Susceptibility is also linked with certain significant histocompatibility complex (MHC) alleles (e.g., human antigen leukocyte [HLA]-DR2) implying that the pathogenesis involves immune mechanisms. The microscopic appearance of the lesions also suggests immune participation. For example, perivascular lymphocytes, macrophages and a large number of CD4+ and CD8 + T cells indicate recurrent MS injuries. CD4 + T cells are also typically occlonal in CSF patients with MS. While a specific antigen is not identified, the data indicate that a particular CNS protein is immunized. The invasive T-cell induced, autoimmune disease, and experimental encephalitis (EAE) provide further assistance for immune systems. While a variety of viruses have been involved in the etiology of MS, no convincing evidence of any infectious agent has been found to date.

The MS mark are demyelinated plaques. In large numbers in the brain and spinal cord (Fig. 32-74) plaques are seldom more than 2 cm high. These are unnoticeable, have seamlessly circular shapes, and typically we see them in the white matter but may reach the gray material. The lesions involve optic nerves, chiasm, para-ventricular white matter, and spinal cord, priority being given to any component of this CNS. Evolving plaques in regions of axonal fairly safeguard, clustering lymphocytes around narrow veins and arteries, macrophage infusion and a substantial edema are distinguished by selective myelin degradation. In plaques, neuronal bodies are significantly untouched, but axons can degenerate. There is a moderate reduction in the number of oligodendrocytes. Plaques are quieter and less edematous as they mature. This series highlights the concentrating essence and selectivity of the wound, as it is completely removed myelin is spread within a plaque Axons usually lose their myelin suddenly within plaques. Dense and gliotic are old lesions of MS plaques.

MS typically starts in the 3rd or 4th decade and is accompanied by rapid medical development outbreaks interrupted by intervals of relative stability. The main clinical criterion for MS is the spread of lesions in space and time; i.e. several separate areas of the CNS have to be affected at different times. The use of serial MRI studies shows persistent active pathology, despite the apparent medical dormancy, revolutionized our perception of disease behavior in MS. Fresh plaques emerge and disappear, triggering medical symptoms. Modern diagnostic criteria for MS include strong imagery to visualize plaques spread over time and space. MS is thus even between clinical dormancy, an ongoing active process. The therapeutic focus of the drug trials and clinical management is ongoing disease activity suppression using diverse immune system modulators such as β-interferon. Enhanced inflamative development in MS patients ‘ brains has resulted in neuropathological tests during aggravations. Most MS clients are on a clinical course relapsing remitting, but some have an unpredictable trajectory without remissions. The formation of additional demyelined MS plaques is affected by all exacerbations. MS typically begins with signs with eye, brain or spinal cord lesions. The symptom also results from blurred vision or vision loss to one eye owing to optic neuritis. Double vision and vertigo occur when the lesion is primary in the brain stem. External ophthalmoplegia, induced by disturbance of medial longitudinal fasciculus, specifically indicates that a young person has demyelinating disease. Acute demyelination is called cross-myelitis when is within the spinal cord and leads to one or both legs ‘ weakness and sensory symptoms in the lower limbs. Many of the first signs are in a couple of months partly reversible. Although the majority of patients have a chronic recurrence and reflectance, neurological defects gradually and relentlessly accumulate. There can be axonal attrition leading to irreversible lesions even in relatively peaceful plaques. The degree of functional impairment, which varies from mild weakness to severe disability and commonly coma, ataxia, extent of visual impairments, incontinence and dementia, is highly variable in defined situations. Air blindness or urinary tract infections usually kill patients with severe MS. After the onset of symptoms, most patients survive 20–30 years.

Source: http://simplybowentherapy.com.au/multiple-sclerosis/ms-types/

1. Reoccurring or relapsing-remitting multiple sclerosis (RRMS). The patient has autoimmune attacks that occur over months, or even years, apart, that trigger the degree of impairment to rise. For instance, a person can lose vision during a bout, but improvement can be followed if there is re-myelination. Unfortunately, the remyelination cycle is more often not complete, however; therefore, a residual deficiency is often left, and, with every strike, the central nervous system is gradually irreversibly impaired. There is usually no change in impairment between ends in the relapse-remitting multiple sclerosis form.
2. Secondary progressive multiple sclerosis (SPMS). Initially quite similar to the RRMS type, but the immune attack is constant over time and causes a constant progression of the disease.
3. Primary-progressive multiple sclerosis (PPMS). This is essentially a continuous attack on myelin that leads to steady disability progression throughout a person’s life.
4. Progressive relapsing multiple sclerosis (PRMS). The illness (MS) is even quicker overlapping with a continuous attack.

In a world where human rights for every person are being discussed and fought for, whether it be a movement for women’s rights, rights for fathers or the LGBT community – this is all becoming normal in society – but what exactly is normal? Normalcy, like many things in the world is misunderstood – some may believe their traditions, values and rules are the norm and are what should be conformed to by everyone – some may have other rules and traditions and so believe otherwise. Normal varies between cultures, generations, religions and countries – it lacks cultural relativism; therefore, my aim is to investigate the idea of normality in a western individualist society such as in the United Kingdom and to the extent in which sufferers can live a ‘normal’ life.

I will explore the effect multiple sclerosis on society and its sufferers, to what extent can patients lead a regular, normal and functional life? Multiple sclerosis is a condition suffered by hundreds of thousands of people each year across the UK. It is an adverse condition that affects the lives of not only the sufferer but their families, relatives, friends and even colleagues. Globally, this degenerative condition affects an estimated 2.5 million people[footnoteRef:1]. Physical impairment, disabilities and debilitating diseases are becoming more common in the United Kingdom, yet the level of awareness and knowledge of these conditions remain the same, parallel to minimal. I firmly believe that social awareness of medical conditions such as ALS, multiple sclerosis and autism is extremely important within societies across the world in order for us to progress as a species. [1: Tim Newman (14th October 2018), Do cannabinoids ease multiple sclerosis symptoms?, Medical News Today, https://www.medicalnewstoday.com/articles/323325.php]

Disease, sickness and health are all normal, but when a person in a wheelchair is seen, or someone with a physical disfigurement is ‘spotted’ – people start talking, in their small groups or pairs begin muttering as if they’ve seen some sort of phenomenon of massive proportions. Why? Society has not been educated, their definition of normal doesn’t include the understanding of disabilities and sickness. Their definition of normal doesn’t include overwhelming diagnoses. No one thing is normal for everything.

What is a normal life?

What is a normal life? It’s a question with many viewpoints, some may argue what a normal life actually is. Death, disease, plague, sickness and fatigue – the normal life of a doctor. Bombs, gunfire, artillery, explosions and loss – the normal life of a soldier. Crying, sick nights, work, family and managing the household – the normal life of a mother. The concept of normal is about as solid as the concept of ‘love’ – misunderstood, complex and varies from person to person. Ideas of normal life varies between cultures. Personally, my normal life in the U.K. was going to sixth form, studying, taking part in sport and spending time with friends – but my perception pf normal life changed when I visited Pakistan in the winter of 2018. I enjoyed the first half of my trip, making little journeys to the local markets and enjoying the scenic drives – that is until my grandmother became comatose and soon passed away, and my mother falling victim to gas poisoning in the next few days: it was then, when trips to the hospital, when nail-biting consultations in front of underqualified doctors in a third-world country became my normal life. Then I came back to the UK, with my mother who’s unwell, and I took up the responsibility of ensuring she took the right medications, right dosages at the correct time; this became my normal life. Normal is a dynamic, fluid – not concrete; a simple traumatic event or a gigantic positive can change what normal is. A person’s ‘normal’ can change in an instant, whether that be from the loss of a close family member to falling victim to a debilitating disease or even a condition such as multiple sclerosis – or on the other end of the spectrum, marriage, bringing someone into your life and vowing to spend eternity with them is a big commitment which changes the course of a person’s entire life.

Normal is an arbitrary term. An abstract concept. In the English Oxford Living Dictionaries, ‘normal’ is defined as: Conforming to a standard; usual, typical, or expected or (for a person) free from physical or mental disorders[footnoteRef:2]. According to this definition, it is impossible for someone with multiple sclerosis to live a normal life, as they are most certainly not free from a physical disorder. ‘Normal’ can’t mean and must not mean ‘what we see all the time’ or ‘what we see the most of.’ It must have a different meaning from that for it to mean anything of value to right-thinking people[footnoteRef:3]. Furthermore, what is the standard that must be conformed to? Who is it set by? Who decides that it’s the standard? Society follows those in power, the media, celebrities, professionals and high earners; the norms of the 1% automatically apply to your average Joe. However, many people (including myself), would thoroughly disagree with this logic – in my eyes, a disease does not get to define whether you can live normally, disease does not determine lifestyle and one social group’s normalities and sociality’s should not be imposed on everyone. Moreover, it is impossible to evaluate what is classified as normal without investigating what is classified as abnormal, as abnormality is the basis for which normalcy is defined. An author by the name of Vincent O’ Sullivan profoundly said: [2: Oxford English Dictionaries, Normal definition (23/01/19), https://en.oxforddictionaries.com/definition/normal ] [3: Eric R. Maisel Ph.D., 2011, What Do We Mean by ‘Normal’?, Psychology Today, 10/03/2019, https://www.psychologytoday.com/gb/blog/rethinking-mental-health/201111/what-do-we-mean-normal]

“If you are different from the rest of the flock, they bite you”[footnoteRef:4] [4: The Next Room, Vincent O’ Sullivan, Tragara Press Edinburgh, 1983]

Conditions such as MS that affect a mere 3.7% of British citizens are quite usually unheard of, therefore society is ready to ‘bite’ at these supposedly unusual people and consequently alienate them for not being ‘normal’, not conforming to their definitions of the term.

Abnormality

Abnormality, like normality, is also an arbitrary term. From a psychological standpoint, someone is classified as abnormal if they deviate from the normalities of their specific societies or fail to function adequately on a day to day basis. Abnormality and normality are so foreign as concepts that there’s a whole branch of psychology known as ‘abnormal psychology’ – to study abnormality often in clinical regards. In my own culture, a person is believed to be abnormal if they aren’t married by a certain age, self-sufficient (if you’re a man) and a skilled housewife (if you’re a woman); however, this an example of cultures in the Middle East. On the other hand, in a western country such as the United States or the United Kingdom, it is quite normal to not be in a relationship, let alone a marriage or civil partnership, it’s quite usual for men to be dependent on people and definitely usual for women to be confident and outgoing. There is a very fine line between abnormality and social normality. Thus, throughout the course of this essay, I will attempt to establish what normality (and inversely, abnormality) is.

What is Multiple Sclerosis?

Humans are interesting organisms; so complex, yet so fragile. Extremely intelligent yet inhibited by their own biology. The human body contains trillions of cells, the human brain alone containing over 86 billion nerve cells. Each nerve cell travelling at a speed of approximately 120 m/s (meters per second)[footnoteRef:5], these cells are of paramount importance to human life, enabling sensitivity, reflex actions and the communication between parts of the brain and the rest of the body. To understand multiple sclerosis, one must first be able to comprehend the neuron. [5: Eric H. Chudler, Neuroscience for Kids, https://faculty.washington.edu/chudler/what.html]

[image: Image result for neuron][footnoteRef:6] The figure displays a basic neuron and its parts. The dendrites carry electrical signals through the cell body to the axon terminals which carry the impulse out of the cell body by releasing chemicals called neurotransmitters – like this information is transferred from one nerve cell to another. The myelin sheath is a fatty tissue which surrounds the axons, thus insulting against the loss of electric current in the nerve cells. [6: Simple English Wikipedia (2018), Neuron, https://simple.wikipedia.org/wiki/Neuron]

Figure

Multiple Sclerosis (MS) is an auto-immune disease, where the body’s own nervous system attacks the myelin sheaths of nerve cells – this means that nerve cells can’t send and receive messages as effectively as they usually would – resulting in a range of symptoms.

Relapsing-Remitting MS

Relapsing-Remitting MS is when patients experience episodes of symptoms, either new or worsening, in periods known as relapses. Over 80% of people diagnosed with MS are diagnosed with relapsing-remitting MS[footnoteRef:7]. Relapses mostly occur without warning and are known to be provoked by periods of stress or illness. Symptoms often worse over days, weeks and months and improve over a similar period of time. Relapse symptoms may fade slowly, with or without targeted treatment or therapies – however some symptoms could persist. The time that passes between relapse attacks are known as periods of ‘remission’ – which can potentially last for years at a time. [7: Paraphrased; NHS Choices (2016), Multiple Sclerosis, https://www.nhs.uk/conditions/multiple-sclerosis/]

Primary Progressive MS

In the primary progressive form of multiple sclerosis, patients begin accumulating symptoms with no periods of remission. 10% of people are diagnosed with this form of multiple sclerosis[footnoteRef:8] and although there are no periods of remission – there are periods where condition appears to stabilise. [8: NHS Choices (2016), Multiple Sclerosis, https://www.nhs.uk/conditions/multiple-sclerosis/]

Multiple Sclerosis in the United Kingdom

There is currently no accurate data on the exact number of people with MS in the UK. A study by McKenzie et al at the University of Dundee worked out a figure based on coding in GP records. This gave a figure of approximately 127,000 people with MS in the UK in 2010. The study also found that the number of people with MS in the UK is growing by around 2.4% per year, due to people with MS living longer[footnoteRef:9]. [9: MS Society (2018), Prevalence and incidence of multiple sclerosis, https://www.mstrust.org.uk/a-z/prevalence-and-incidence-multiple-sclerosis] [10: Based on statistics obtained from: Multiple Sclerosis Trust (2010), Prevalence and incidence of multiple sclerosis, https://www.mstrust.org.uk/a-z/prevalence-and-incidence-multiple-sclerosis]

Symptoms and Struggles

Have you ever suffered from a cold? Seasonal allergies? Bacterial or viral infections? It’s a part of life, pathogens – almost a thousandth the size of a millimetre capable of rendering a person bedridden for days, weeks and sometimes months. Aches, pains, headaches and migraines, yet all your bodily systems completely intact. Now imagine losing a part of yourself, a system essential for the processes you carry out every day of your life – the nervous system. Multiple sclerosis patients experience many symptoms and struggles in their daily life such as, but not limited to:

• Fatigue
• Problems with vision
• Mobility problems
• Depression and anxiety

Waking up, every morning – some mornings being able to operate perfectly, others, not being able to come out of bed yourself. Some mornings, using your sense of vision – a sense taken for granted – other mornings waking up with blurry vision; however, that’s only the physical side of it. Depression and mental health take its own toll as well. Multiple sclerosis patients experience these struggles, and many more, on a regular basis.

Interviews with MS Patients

In order to truly understand the extent of someone’s suffering, it has to be put into terms one can understand and internalise for themselves. An interview with an MS patient by the name of Trevis Gleason really helped my understanding of the sort of struggles he faces with his multiple sclerosis when he was asked ‘In what order would you prefer your symptoms to be resolved’, Mr Gleason simply replied with ‘You know, that’s kind of like the question, “What would you change in the world?” My answer to that is “poverty.” Without abject poverty in the world, so many other problems could be solved. As to MS, I think I could “do” so much more for my MS if I could resolve my issues with fatigue’[footnoteRef:11]. From my understanding, Trevis Gleason feels as if his fatigue is disabling him from taking steps to further [11: Trevis Gleason, 2009, An Interview with Trevis Gleason About his Multiple Sclerosis, Everyday Health, 10/03/2019, https://www.everydayhealth.com/columns/trevis-gleason-life-with-multiple-sclerosis/an-interview-with-trevis-gleason-about-his-multiple-sclerosis/]

Introduction

Multiple Sclerosis (MS) is an inflammatory, demyelinating and debilitating autoimmune disease of the central nervous system (CNS),with Overcoming Woman gender which without effective cure and requires Lifetime treatment(1).

The purpose of Treatment in MS is to prevent recurrence and reduce the rate of neurologic Destruction.(2). Doctors generally prescribe disease-modifying drugs (DMDs) to reduce the frequency and severity of relapses in Multiple Sclerosis(3). DMDs (injectable drugs)contains IFN β-1a, IFN β-1b, Glatiramer acetate, Rituximab, Mitoxantrone, Natalizumab .The reported side effects of interferons include , alopecia and flu like syndrome ,mild anemia, variation of transaminases ,Local reaction and cutaneous necrosis, at the injection site, erythematous reactions , Necrotizing vasculopathic skin lesions, neuropathy, increase in spasticity ,livedo- reticularis and digital necrosis, Arthritis ,depression, and suicidal ideation ,headaches, Pneumonia(4-6)

The reported side effects of Glatiramer acetate include, nausea or vomiting skin rashes rapid heart rate, depression ,skin color changes, ,weight gain, anxiety, , body pain and weakness ,flushing ,breathing difficulties ,chest pain and (7).

The reported side effects of Mitoxantrone include, headache, heartburn, , diarrhea, nausea, vomiting constipation, unusual tiredness heavy menstrual bleeding, alopetia, , missed menstrual periods, runny nose, depressed mood(8).

The reported side effects of Rituximab include, fever, headache, nausea , diarrhea, heartburn flushing, weakness, chills stomach pain muscle or joint pain back pain ,dizziness(9).

The reported side effects of Natalizumab include joint or muscle pain, headache swelling hands/feet/ankles, redness or irritation at the injection site, skin rash changes in menstrual cycle, painful menstrual cramps diarrhea, depression, or cold symptoms, chest pain(10).

Due to the importance of adverse effects In clinical practice in the choice of medication Therefore, DMDs complications are compared in this article.

Materials and methods

Three hundred and sixteen MS patients (38male and 278 female) who were treated with DMDs (injectable drugs)contains IFN β-1a, IFN β-1b, Glatiramer acetate, Rituximab, Mitoxantrone, Natalizumab for at least 2 years were studied with cross sectional design (Patient checkup at a specified time interval (6-12 months).129. patients were treated with IFN β-1a and 49 patients were treated with IFN β-1b ,67 patients were treated with Mitoxantrone and 25 patients were treated with Rituximab and 16 patients were treated with Natalizumab and 30 patients were treated with Glatiramer acetate

Study populations were clinically definite MS patients who were consulted in Imam Khomeini clinic or in Sina hospital in Hamadan city.

At first clinically definite MS patients who were treated with Injectable DMDs for at 2 years patients in whom administration of drug were resulted in side effects, were evaluated. Clinical course and test results and MRI findings were reviewed (in 3-6-12-24 months intervals) by a competent neurologist and pharmacist.

Entry criteria included patient of 15–50 years with a clinical- or laboratory-supported diagnosis of relapsing MS and Secondary Progressive Multiple Sclerosis (11) should also have an Expanded Disability Status Scale(EDSS) 0-5 (12).Patients with EDSS above 5, were excluded from the study. Exclusion criteria included history of severe allergic or anaphylactic reaction to any DMD, or to other components of drug formulation, no evidence of , , cardiac, hepatic, renal, psychiatric, cancer , neurologic, hematologic ,auto-immune diseases, chronic diseases, endocrinologic, history of epilepsy و suicidal ideation , severe depression, enrollment, lactation and pregnancy as determined by history, physical examination, and screening blood tests.. Tenets of current version of the Declaration of Helsinki were followed, institutional ethical committee approval was granted, and the nature of the trial and possible side effects of the drugs were explained to the patient. After a detailed discussion with the neurologist, patients made a final decision and each patient signed an informed consent. All 316 patients performed their treatment without interruption. To assess side effects, a questionnaire was prepared (in 3, 6, 12, 24 months intervals) completed for each patient. Eventually.The frequency of side effects was determined for each group and the collected data were compared in each treatment group.

1. Edan G, Miller D, Clanet M, Confavreux C, Lyon-Caen O, Lubetzki C, et al. Therapeutic effect of mitoxantrone combined with methylprednisolone in multiple sclerosis: a randomised multicentre study of active disease using MRI and clinical criteria. Journal of Neurology, Neurosurgery & Psychiatry. 1997;62(2):112-8.
2. Randomised double-blind placebo-controlled P. study of interferon beta-1a in relapsing/remitting multiple sclerosis. PRISMS (Prevention of Relapses and Disability by Interferon beta-1a Subcutaneously in Multiple Sclerosis) Study Group. Lancet. 1998;352(9139):1498-504.
3. O’Brien JA, Ward AJ, Patrick AR, Caro J. Cost of managing an episode of relapse in multiple sclerosis in the United States. BMC health services research. 2003;3(1):17.
4. Zivadinov R, Zorzon M, Tommasi MA, Nasuelli D, Bernardi M, Monti-Bragadin L, et al. A longitudinal study of quality of life and side effects in patients with multiple sclerosis treated with interferon beta-1a. Journal of the neurological sciences. 2003;216(1):113-8.
5. Montalban X, Durán I, Rio J, Saez-Torres I, Tintoré M, Martínez-Cáceres E. Can we predict flu-like symptoms in patients with multiple sclerosis treated with interferon-β? Journal of neurology. 2000;247(4):259-62.
6. Loftis JM, Hauser P. The phenomenology and treatment of interferon-induced depression. Journal of affective disorders. 2004;82(2):175-90.
7. Johnson KP, Brooks B, Cohen J, Ford C, Goldstein J, Lisak R, et al. Extended use of glatiramer acetate (Copaxone) is well tolerated and maintains its clinical effect on multiple sclerosis relapse rate and degree of disability. Neurology. 1998;50(3):701-8.
8. Crossley RJ, editor Clinical safety and tolerance of mitoxantrone. Seminars in oncology; 1984.
9. Kimby E. Tolerability and safety of rituximab (MabThera®). Cancer treatment reviews. 2005;31(6):456-73.
10. Polman CH, O’connor PW, Havrdova E, Hutchinson M, Kappos L, Miller DH, et al. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. New England Journal of Medicine. 2006;354(9):899-910.
11. Poser CM, Paty DW, Scheinberg L, McDonald WI, Davis FA, Ebers GC, et al. New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Annals of Neurology: Official Journal of the American Neurological Association and the Child Neurology Society. 1983;13(3):227-31.
12. Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983;33(11):1444-.

It is that time to talk about multiple sclerosis and what it is. What is it and what does it do to the human body and the ones affected by it? Multiple sclerosis is a rare disease it happens to be about 200,000 US cases per year. Multiple sclerosis tends to affect women more than men. So, what is the disease about, the symptoms and treatment.

MS is a disease in which the immune system eats away the protective covering of the nerves. It is a disease that affects the central nervous system which is composed of two principal parts, those two parts are the brain and spinal cord. In some way this disease stops the communication between the body and brain. Multiple sclerosis affects every individual differently some people’s symptoms are dormant and still have not experienced anything some have flares of symptoms and others have severe forms of MS. For example, “When myelin or nerve fibers are damaged or destroyed in MS, messages within the CNS are altered or stopped completely”. Since damage has occurred in the central nervous system (CNS) it causes various neurological symptoms. Those symptoms will depend on the person who has multiple sclerosis because it depends on the type of MS and how severe or not the disease is. The damaged areas tend to develop scar tissue that is what gives MS its name because it is basically multiple areas of scarring in the central nervous system. Researchers of the disease do not know what causes it but believe it has to do with something genetic so something that is abnormal in the affected immune system or who knows it can also be something environmental that can possibly trigger the disease.

The symptoms that people tend to have are endless and may seem “normal” but shouldn’t be ignored because one never knows what it can possible be. The main things people tend to experience are pain, tremors, sensory, urinary, sexual, mood, visual, whole body, muscular and lastly speech. The pains are felt possibly in yours eyes or back. For instance, if you do a sudden movement like a head nod it causes back pain. Tremors in your hands and legs when you do certain movements. Sensory meaning like feeling “stars” on legs or the feeling of pins and needle or reduced sensation. Urinary like leaking during the night or maybe retention or the excessive urge depends on the person. Sexual meaning like men can experience erectile dysfunction. You may experience anxiety or other mood swings as well. Visually you may experience double vision, blurred or vision loss too. The whole-body meaning loss of balance, fatigue vertigo etc. Muscular problems are endless in this case. For example, cramping, involuntary movements or muscle paralysis etc. Lastly, the speech is affected like your speech gets slurred and just have a really hard time talking. Multiple sclerosis is such a body damaging disease that it is unbelievable to me how people can live with it. The symptoms and the severity of them depends on each person.

The treatments that can be done are not a lot but can help. First of all, the main person the person suffering from this disease has to seek is the help of a Neurologist because if they do not how will you get treated. What the neurologist will do is help you get help from other specialist such as speech therapist, physical and occupational therapist and phycologist as well. The treatments consist of immunosuppressants such as steroids to reduce inflammation or a simple anti-inflammatory. Another treatment can be a immunosuppressive drug or chemo too. That is just medication treatment, but one can seek counseling or group/support therapies that maybe beneficial to one’s emotional health which is important.

Overall, I feel like I learned everything that I needed to learn from multiple sclerosis. I learned what it is a disease that affects the body’s central nervous system which is composed of two parts which are the spinal cord and brain. I learnt about all the possible symptoms that depending on the persons severity of the disease it will cause them to experience such as muscle paralysis, cramps and tremors and problems with speech. It is sad to know that they still haven’t found what causes it that there is still no cure for it. What I would tell the public about this topic that is multiple sclerosis is if you feel that it resonates with you and possible things you might me experiencing go get checked because it is better to know than to be unaware of it and suffering. If some people do not have the severe symptoms and have noticed that they get certain symptoms occasionally go, get examined because you never know. Do your research and take care of your body. Your body will let you know when something is wrong so be aware of what it tells you learn to understand it.

Multiple sclerosis (MS) is a disabling disease of the central nervous system that mainly affects people in their young age. Pathogenic mechanisms that bring about the development of multiple sclerosis (MS) have yet to be clearly identified, but considerable evidence indicates autoimmunity plays an important role in its etiology. Autoimmune diseases like MS are postulated to arise from complex interactions between individual genetic susceptibility and environmental factors. Previous infection with Epstein-Barr virus, vitamin D insufficiency and smoking are established risk factors for developing MS.

Environmental effect on development of MS is strongly suggested by its geographic distribution. Prevalence rates are higher in regions in higher latitudes and lower near the equator. The effect of latitude is largely through the exposure to sunlight and Vitamin D synthesis in the body. Most epidemiological studies focusing on the impact of sun exposure and vitamin D levels in MS development have focussed on Caucasian populations. Migration studies, have shown changes in the risk of MS in people who migrate between areas that have different environmental risk factors.

Another environmental factor that can act as environmental triggers inducing or promoting autoimmunity, are microbial infections. Infectious diseases might also accelerate established, but sub-clinical, autoimmune processes. Chicken pox (Varicella zoster virus -VZV) is a neurotrophic virus that remains in the nervous system for decades and has been hypothesised as a possible agent in MS pathogenesis, but results from most epidemiological or serological studies are insufficient to support an association between MS and VZV infection. Recent studies have reported large amounts of VZV DNA inside blood lymphocytes and CSF from MS patients during acute relapses, which disappeared from the CSF in the same patients during phase of remission. These findings support direct participation of VZV in MS etiology, possibly through host virus interaction.

Both active and passive cigarette smoking and MS risk have demonstrated a dose-dependent relationship. Increased risk is associated with cumulative smoking which is reflected by serum levels of nicotine. This risk subsides after a decade of smoking cessation. Case control studies have shown an estimated 40-80% increased risk of developing MS.Smoking prevention and cessation integrated with other treatment strategies might be a reliable and effective way to improve MS outcomes.

The association between breastfeeding and MS has so far been investigated in few studies, which yielded contradictory results. Spencely and Dick found no association between breastfeeding and MS risk,16 whereas in a study comparing patients with MS who were breastfed for 8.4 months with controls who were breastfed for 12.5 months. Pisacane et al. showed an association between prolonged breastfeeding and decreased risk of MS.

The incidence of MS has been increasing rapidly in many countries, including countries of the Arabian Gulf (currently 31-55 per 100000). Recent studies from Saudi Arabia have reported an increased prevalence, however all the studies are hospital based and do not account for underdiagnosed ing that the inconsiderisease.

Considering that the increase in prevalence of MS has occurred over a short period of time it is likely that environmental factors play a more important than genetic factors. Unlike genetic risk factors, many environmental and lifestyle factors are modifiable and most regions around the globe, especially the gulf countries have exhibited remarkable socio-economic and lifestyle changes in past few decades.

With a reported increase in the incidence globally as well as in the middle eastern region, there is an urgent need to understand the role of modifiable factors traditionally implicated in the causation of MS. Information on these factors which could have a role in disease-causation as well as protection could be incorporated into patient care and into preventive programmes, particularly for individuals with a positive family history of MS and therefore increased risk of developing the disease. Observational and prospective studies in the region are of fundamental importance to confirm or rule out this association.

Multiple sclerosis (MS) is a progressive neurological disease of the central nervous system (CNS) and its pathogenesis has been associated with auto-immune mechanisms underlying the inflammatory demyelination of neurons. Myelin is the sheathed coating of neurons which provides multifaceted functions like neuroprotection and enhances synaptic transmission throughout brain regions. Therefore, the pathological demyelination of neurons results in distorted, slow or even the absence of neuronal communication. This consequently leads to the onset of many symptoms that characterise MS. Symptoms include mobility complications, muscle fatigue, spasms, involuntary eye movement, double vision and temporary blindness in one eye (optic neuritis).

Although the exact underlying cause of the condition remains unknown, research has found links between the onset of MS and inflammation. Microglia are the main inflammatory cells of the CNS and can detect neural lesions and demyelination. Neuronal regions and white matter of the CNS are protected from the actions of the peripheral immune system due to the blood-brain barrier. Despite this anatomical division, the infiltration of T-cells into the CNS, due to signalled recruitment from microglia, can occur. This activation and migration of immune cells causes the release of inflammatory mediators such as cytokines, as well as further migration of other immune cells like macrophages and B-lymphocytes from the peripheral immune system. Antibodies cause tissue destruction and the release of intermediate products from macrophages elicit detrimental oxidative stress. Such products include nitrogen and reactive oxygen species, found to be linked to hypoxia through impaired mitochondrial functioning. Increased inflammation of the brain ultimately can result in extensive demyelination of white matter, axonal degeneration, preventative axonal regeneration and neuronal cell death. It is yet to be determined whether the process of demyelination precedes or follows inflammation and neurodegeneration.

It has been found that MS is the most common neurological condition that young adults suffer from in the Western countries (Lassman et al). About 2,500,000 cases of MS have been reported globally, and prevalence rates in the England alone is around 164 per 100,000. Incidence rates tend to highlight that countries farther from the equator (both at a Northern or Southern distance) such as Scotland have higher MS rates. Geographical discrepancies in the epidemiology of MS imply that perhaps there are genetic factors as well as environmental effects that contribute to the susceptibility of tissue damage across individuals. Environmental factors include smoking, suggested to adversely hinder disease outcomes.

There is no cure for MS. Thus, treatments aim to prevent symptomatic relapse or further progression of the condition. Variance in symptom severity has determined the difference in treatment options prescribed to individual MS sufferers. Corticosteroid treatment, such as oral methylprednisolone, is prescribed for five days in the early presence of mild relapses. New lesions (active MS), indicated through MRI scans, tend to be treated with beta interferons. These drugs are used to reduce inflammation within the CNS.

However, draw-backs of steroid treatment for treating relapse in MS include short-term side effects like insomnia, altered mood, chest-pain and palpitations. Long-term treatment can cause weight gain and osteoporosis, consequently leading to further health implications and reduced quality of life.

Current drugs are being developed to tackle the symptoms that underlie different types of MS. An example includes Laquinimod. Research into this tablet found that it can possibly alter the activity of immune cells and therefore prevent their infiltration across the blood-brain barrier. This information subsequently implied that Laquinimod can possibly reduce neuroinflammation in the white matter as well as protect cells in the brain.

Despite these promising findings, in 2014 Laquinmod was declined at trial phase 3 stage to treat relapsing MS. Further investigations are currently being undertaken in another phase 3 trial and results of Laquinmod on relapsing MS is expected in 2019. However, the once daily tablet is now also being considered to treat primary progressive MS symptoms and currently being developed within a phase 2 trial. The effectiveness of this drug treatment shall be assessed by observing MRI scans to detect changes in brain volume and the occurrence of new neuronal lesions after administration. Low-dosage introduction of the tablet was well tolerated in trial subjects.

Moreover, investigations exploring antihistamine drug mechanisms have discovered that these compounds can also significantly influence immune response. It has been found that Clemastine fumarate, an active constituent of many antihistamine drugs, can enter the central nervous system and can use drowsiness. The side effects of drowsiness and dizziness are common, particularly when antihistamine drugs are prescribed for conditions such as hay fever. Therefore, Clemastine fumarate’s transport capability, across the blood-brain barrier, highlighted promising potential of the drug in treating neurological conditions like MS.

Phase 1 trials conducted in 2010 found that subjects who had their immune cells injected with the Clemastine showed reduction in cellular activity and can promote myelin repair after pathological demyelination. It is currently in phase 2 trial testing for relapsing MS due to its immunosuppressive competence and potential therapeautic effects in other conditions. However, the compound is yet to be administered in MS sufferers. Therefore, the true extent of possible side effects for MS patients remains unknown and requires further investigation.

Furthermore, prevalent aspects of the condition such as neuronal cell death and axonal degeneration, are also being considered in drug discovery. Ibudilast (MN-166) is undergoing development for progressive MS. This drug is a phosphodiesterase inhibitor and its proposed mode of action is to reduce inflammatory activity in order to prevent neural cell deficiency. It can conduct this function by supressing pro-inflammatory cytokines. Phase 2 trial investigations suggested that though Ibudilast did not impact distinct lesion occurrence and subsequent relapsing MS, neuroprotective capabilities were evident through the reduced progression of MS in subjects.

As previously mentioned, the release of reactive oxygen species, from migrated immune cells, in the CNS can pathologically exacerbate MS symptoms. Research conducted to tackle this biological target has found that common antioxidants like Lipoic acid (LA) can reduce inflammation. Damage to the myelin sheath is thought to proceed the autoimmune attacking of myelin by T-cells, resulting in heightened inflammation. LA provides a significant proposition in treating symptoms of MS. It can potentially modulate the immune response as well as yield anti-inflammatory effects in order to provide neuroprotection.

A pilot study published in the Multiple Sclerosis journal (2005) found that oral LA administration reduced the levels of T-cell migration into the CNS in 37 sufferers. LA was well tolerated and absorbed. This further implies the effectiveness of LA as prime MS treatment. Following this, the oral drug has undergone another pilot study, a phase 1 trial completed in 2016 and is currently in phase 2 trial status. The phase 2 trial has begun in 2017 and will be longitudinal in order to assess mobility of sufferers after two years.

However, the use of LA in other conditions has shown side effects such as muscle cramps and headaches. The risk of muscle cramps in particular may deter MS patients from using this medication due to the belief that this symptom can aggravate others of their disease such as motility. Furthermore, the high-dosage of orally administered LA in the trial (1,200mg) highlights the drug’s lower potency. This can also cause issues with patient compliance as it may require treatment to be administered through multiple oral tablets a day, rather than just one.

Moreover, LA still does have significant beneficial potential over existing treatments. It was found in 2016 that the drug can also reduce brain atrophy, implying a neuroprotective role. Advantageous potential of this drug intervention is that it is dual-tackling. This includes modulation of immune cell activity but also potential rehabilitation of anatomical damage in MS. This suggests preventative measures for onset as well as blocking further degeneration. Therefore, this evidence illustrates that LA is the best possible treatment for this neurological condition. This is due to the multiple action that LA can exhibit, in comparison to other compounds that only target individual aspects of the condition.

Multiple Sclerosis, widely referred to as MS, is a lifelong, progressive medical condition that affects the central nervous system. There are currently around two million people worldwide that suffer from the condition and it is currently incurable. It affects both white and grey matters of the CNS and it’s underlying neuropathology leads to loss of myelin/oligodendrocyte complex, as well as neuronal and axonal degeneration. It can cause minor or serious disability, and although it may be possible to treat the symptoms, MS sufferers also have a slightly reduced average life expectancy. The condition is most commonly diagnosed within people in their 20s and 30s, however it may develop at any age, and it is more commonly found in women than men.

The National Institute of Neurological Disorders and Stroke in the United States report that vision problems are often the initial symptom of MS. This is due to inflammation affecting the optic nerves. Changes in vision include, blurriness, double vision, colour-distortion, loss thereof and pain when looking up or to the side. Other symptoms include; weakness and fatigue, tingling and numbing sensations within the arms, legs, fingers and face, pains (both short and long term) and spasms, and dizziness or loss of balance. The vast majority of people with MS also experience some degree of bladder dysfunction. Bladder issues occur when lesions affect nerve signals that control the bladder and urinary function.

Although the aetiology of multiple sclerosis is elusive, the pathogenesis has been derived from the basic CNS tissues of MS patients. There is still ongoing research into the autoimmune nature of MS, however it is well established that the immune system participates in the destruction of myelin and nervous cells. The destruction of myelin (demyelination), inflammation, and potential defects in synaptic transmission and putative circulating blocking factors are the main causes of the negative symptoms associated with MS.

Despite the disease process in multiple sclerosis appearing to be directed mainly against glial cells, the clinical features arise primarily from the electrophysiological consequences for axons. This can result in many different effects, from axonal hyperexcitability, spontaneous generation of spurious ectopic impulses, and even a complete conduction block. While the conduction block arises from factors such as demyelination, hyperexcitability represents a maladaptive response to demyelination, involving an inappropriate balance of ion channels across the segment of the demyelinated membrane. In MS, myelin-forming oligodendrocytes are the targets of inflammatory and immune attacks. OLG death by apoptosis or necrosis causes the cell loss seen in MS plaques.

Plaques of inflammatory demyelination within the central nervous system are the pathologic hallmark of multiple sclerosis, and the myelin destruction is a vital element of this plaque. Lesions are comprised of many pathologic and immunologic features. Acute MS plaque represents the earliest stage of lesion formation. It is characterised by inflammatory infiltration, combined with demyelination which is distributed throughout the lesion. Typical features of the acute plaque include ill-defined margins of myelin loss, infiltration of immune cells and parenchymal edema. The constituents of immune cell influx around vessels (termed perivascular cuffing) include lymphocytes (predominantly T cells), monocytes and macrophages. A portion of major histocompatibility class II (MHCII)-expressing cells that are distributed evenly throughout the lesion, are loaded with lipids and participate in actively stripping the myelin from axons. While oligodendrocyte apoptosis has been observed the degree of oligodendrocyte loss within active lesions can be variable. Complement C5 promotes axon preservation and new myelin formation, which protect OLGs from apoptosis. These findings indicate that activated complement C5b-9 plays a proinflammatory role in acute MS but may also protect OLGs from death in chronic MS. Glial reactivity throughout the lesion is noted, particularly hypertrophic astrocytes. However, dense glial scarring is not typical of the acute plaque.

Inflammatory mediators, such as axonal degeneration, and synaptic dysfunction resulting from cortical lesions are also large contributors towards the pathophysiology of multiple sclerosis. Specifically, these can be linked to some of the more major functional deficits, such as numbness, paralysis and blindness. The variety in the symptoms of multiple sclerosis can be partly explained due to the conduction properties of affected axons, though the explanation for these are mainly anatomical. This is due to the distribution of lesions in different patients, meaning that a magnitude of separate pathways are disturbed, which results in the diversity of the symptoms.

The main cause of relapse or remission of multiple sclerosis (loss of function) is the failure of axonal conduction at the site of a lesion. Function is lost frequently in inflammatory demyelinating lesions, as several mechanisms are operating, each of which can be a contributing factor towards conduction block. Other causes of remission can arise from a range of mechanisms. including restoration of conduction due to the resolution of inflammation, axolemmal plasticity restoring conduction to the demyelinated axon, adaptive synaptic changes, and repair by remyelination. Unfortunately, over time these compensatory processes become less effective and axonal degeneration becomes a more dominant issue.

Microglia are the intrinsic immune cells in the CNS; they play an important role in the processes of demyelination and remyelination in multiple sclerosis. Microglia can function as antigen-presenting cells and phagocytes. Microglia were once considered to be the same cell type as macrophages. Microglia express major histocompatibility (MHC) antigens I and II and secrete many proinflammatory and anti-inflammatory cytokines such as interleukin-1 (IL-1), tumor necrosis factor-α (TNF-α), and IL-10.

It has been observed that the type of microglial cell and of astrocyte activation and proliferation observed suggests that CNS cells contribute and also may play a critical role in disease progression. Astrocytes could contribute to this process through several mechanisms. This could be as part of the innate immune system, as a source of cytotoxic factors, inhibiting remyelination and axonal regeneration by forming a glial scar, or by potentially contributing to axonal and mitochondrial dysfunction. Furthermore, regulatory mechanisms that are mediated by astrocytes can be affected by aging. Astrocytes may also limit the detrimental effects of pro-inflammatory factors, while providing both support and protection for the oligodendrocytes and neurons.

Interferon- β 1b was introduced in 1993 as the first FDA-approved treatment for multiple sclerosis. This began an era of treatment for this incurable disease, and its natural course was permanently changed. Currently, there are seven different treatments for patients with multiple sclerosis with different mechanisms of action and dissimilar side effect profiles exist. These medications include interferon- β 1a intramuscular (Avonex), interferon- β 1a subcutaneous (Rebif), interferon- β 1b subcutaneous (Betaseron/Extavia), glatiramer acetate (Copaxone), natalizumab (Tysabri), Fingolimod (Gilenya), teriflunomide (Aubagio), and mitoxantrone aka Novatrone.

Avonex was approved by the FDA in 1996 in order to treat patients that were relapsing with MS. It came however with multiple side effects, including flu like symptoms, or less commonly the causation of the deterioration of psychiatric disorders.

Rebif is commercially available at two doses and is administered three times weekly.

In 1993, Betaseron was the first immunomodulatory agent approved by the FDA for the treatment of patients with RRMS ((Relapsing-Remitting Multiple Sclerosis.) It is also approved however, for the treatment of patients suffering with SPMS (Secondary progressive MS.) Copaxone is a synthetic polymer of random sequences of four naturally occurring amino acids and is used as one of the first line disease modifying agents for the treatment of RRMS.

Tysabri is a humanised anti-integrin monoclonal antibody that has been utilised in order to treat patients suffering with RRMS and it is administered once every 28 days via IV at a strength of 300mg. It works by targeting the α4 chain of α4- β1 integrin. All leukocytes except for neutrophils express VLA 4 on their surface, which binds to the adhesion molecule on the surface of activated cerebral endothelial cells. This is a crucial step in the transendothelial migration of leukocytes to the CNS.

Gilenya was approved for treatment of MS in 2010. It is promoted as a second-line drug however, as it resulted in complications during the clinical trial, when two patients contracted herpes zoster infection. This resulted in two of the patients’ death. Novatrone has immuno-supressive features and intercalates with DNA, this in turn causes single and double stranded breaks. It also supresses the DNA repair by inhibiting topoisomerase.

In addition to the trove of medicines that are already available for patients suffering with MS, there are also a large number of clinical trials being conducted to assess the safety and efficacy of other experimental drugs. An example of one of these drugs is Rituximab. Rituximab (Rituxan) is a chimeric monoclonal antibody with IgG1 heavy-chain and kappa light chain constant region which depletes CD20+ B lymphocytes via cell-mediated and complement-dependent cytotoxic effects, while also promoting the apoptosis of these cells. In 1997, the FDA approved use of rituximab for the treatment of relapsing or refractory cases of low grade CD20+ B lymphocyte non-Hodgkin lymphomas. CD20 antigen is a 35 kDa transmembrane protein which is expressed by majority of B lymphocytes in patients with non-Hodgkin lymphomas. While normal B lymphocytes and its precursors express this antigen, plasma cells, T lymphocytes, and hematopoietic stem cells do not possess CD20 antigen. As a B lymphocyte depleting drug, administration of rituximab leads to rapid abolition of CD20+ B lymphocytes in the peripheral circulation. One phase 2 clinical trial assessed efficacy of rituximab in patient with relapsing-remitting MS, and results of this study indicated that treatment of MS with rituximab was associated with decline of contrast-enhancing lesions versus the placebo as well as significant reduction in risk for relapse.